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Cited by 101Psychosomatic Disorders and Their TreatmentsEmbodied and Extended CognitionNeural and Behavioral Psychology Studies

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An insula hierarchical network architecture for active interoceptive inference

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Fermin, Alan S. R., Friston, Karl, Yamawaki, Shigeto·2022·Royal Society Open Science
DOI 10.1098/rsos.220226PMC PMC9240682
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Abstract

In the brain, the insular cortex receives a vast amount of interoceptive information, ascending through deep brain structures, from multiple visceral organs. The unique hierarchical and modular architecture of the insula suggests specialization for processing interoceptive afferents. Yet, the biological significance of the insula's neuroanatomical architecture, in relation to deep brain structures, remains obscure. In this opinion piece, we propose the Insula Hierarchical Modular Adaptive Interoception Control (IMAC) model to suggest that insula modules (granular, dysgranular and agranular), forming parallel networks with the prefrontal cortex and striatum, are specialized to form higher order interoceptive representations. These interoceptive representations are recruited in a context-dependent manner to support habitual, model-based and exploratory control of visceral organs and physiological processes. We discuss how insula interoceptive representations may give rise to conscious feelings that best explain lower order deep brain interoceptive representations, and how the insula may serve to defend the body and mind against pathological depression.

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Figures

Figure 1. (a) Basic organization of neural pathways linking the parasympathetic and sympathetic branches of the autonomic nervous systems to the insular cortex and their effects on visceral functions. (b) Schematic diagram of ascending interoceptive pathways to the insula. (c) Distinct cortical and striatum connections that predominantly target each insula modular cytoarchitecture. gINS (granular insula), dINS (dysgranular insula), aINS (agranular insula), VMb (ventromedial basal thalamus nuclei), VMpo (ventromedial posterior thalamus nuclei), PV (paraventricular thalamus nuclei), HYP (hypothalamus), PBN (parabrachial nucleus), PAG (periaqueductal gray), NTS (nucleus tractus solitarius), AP (area postrema), NAMB (nucleus ambiguus), MRF (medulla and reticular formation), STT (spinothalamic tract), TGC (trigeminal complex), TGT (trigeminal thalamic tract), PPTN (pedunculopontine tegmental nucleus), BNST (bed nucleus of the stria terminallis), LC (locus coeruleus), DR-MR (dorsal raphe and median raphe), VTA-SNc (ventral tegmental area and substantia nigra pars compacta), NBM (nucleus basalis of Meynert), Str (striatum), Hip (hippocampus), Amyg (amygdala), Hb (habenula), pStr (posterior striatum), dStr (dorsomedial striatum), vStr (ventral striatum), SMG (supramarginal gyrus), SMA (supplementary motor area), STG (superior temporal gyrus), DLPFC (dorsolateral prefrontal cortex), MOFC (medial orbitofrontal cortex), MAPFC (medial anterior prefrontal cortex).
Figure 1. (a) Basic organization of neural pathways linking the parasympathetic and sympathetic branches of the autonomic nervous systems to the insular cortex and their effects on visceral functions. (b) Schematic diagram of ascending interoceptive pathways to the insula. (c) Distinct cortical and striatum connections that predominantly target each insula modular cytoarchitecture. gINS (granular insula), dINS (dysgranular insula), aINS (agranular insula), VMb (ventromedial basal thalamus nuclei), VMpo (ventromedial posterior thalamus nuclei), PV (paraventricular thalamus nuclei), HYP (hypothalamus), PBN (parabrachial nucleus), PAG (periaqueductal gray), NTS (nucleus tractus solitarius), AP (area postrema), NAMB (nucleus ambiguus), MRF (medulla and reticular formation), STT (spinothalamic tract), TGC (trigeminal complex), TGT (trigeminal thalamic tract), PPTN (pedunculopontine tegmental nucleus), BNST (bed nucleus of the stria terminallis), LC (locus coeruleus), DR-MR (dorsal raphe and median raphe), VTA-SNc (ventral tegmental area and substantia nigra pars compacta), NBM (nucleus basalis of Meynert), Str (striatum), Hip (hippocampus), Amyg (amygdala), Hb (habenula), pStr (posterior striatum), dStr (dorsomedial striatum), vStr (ventral striatum), SMG (supramarginal gyrus), SMA (supplementary motor area), STG (superior temporal gyrus), DLPFC (dorsolateral prefrontal cortex), MOFC (medial orbitofrontal cortex), MAPFC (medial anterior prefrontal cortex).CC BY · PubMed Central
Figure 2. (a) Hierarchical insula, prefrontal cortex and striatum parallel networks for active interoceptive inference. In the IMAC model, parallel neuroanatomical networks linking the insula with the PFC and striatum, supported by the acetylcholinergic and dopaminergic systems, are specialized for distinct functions related to active interoceptive inference, such as interoceptive introspection, interoceptive prediction, interoceptive selection, interoceptive precision and interoception flexibility. The insula-PFC-striatum parallel networks are hierarchically organized as follows. The lower level comprises the gINS-SMA-pStr network specialized for storage and quick generation habit-like interoceptive predictions. The mid-level comprises the dINS-DLPFC-mStr network specialized for model-based interoceptive predictions, and the highest level comprises the aINS-VMPFC-vStr network specialized for interoceptive exploration. Other neural systems provide additional functions to the interoceptive predictions of these networks, such as supervised interoceptive predictions by the cerebellum, social interoception by the TPJ, episodic interoception and declarative interoception by the hippocampus, and Pavlovian interoception conditioning by the amygdala. The dashed line represents ascending interoceptive prediction errors. The continuous lines represent descending interoceptive predictions. The black lines represent connections within the striatum circuitry. (b) Schematic representation of the neuroanatomical location of the brain structures supporting insula active interoceptive inference. SMA (supplementary motor area), DLPFC (dorsolateral prefrontal cortex), VMPFC (ventromedial prefrontal cortex), ACC (anterior cingulate cortex), gINS (granular insula), dINS (dysgranular insula), aINS (agranular insula), pStr (posterior striatum), mStr (dorsomedial striatum), vStr (ventral striatum), eGP (external globus pallidus), iGP (internal globus pallidus), THA (thalamus), vlSN (ventrolateral substantia nigra complex), mSN (medial substantia nigra complex), VTA (ventral tegmental area), SNc (substantia nigra pars compacta), CB (cerebellum), NTS (nucleus tractus solitarius), D1 (dopamine receptor of the direct pathway), D2 (dopamine receptor of the indirect pathway), BS (brainstem), SB (subcortical brain regions, e.g. amygdala), vTHA (visceral thalamus: VMpo, VMb, PV [figure 1]).
Figure 2. (a) Hierarchical insula, prefrontal cortex and striatum parallel networks for active interoceptive inference. In the IMAC model, parallel neuroanatomical networks linking the insula with the PFC and striatum, supported by the acetylcholinergic and dopaminergic systems, are specialized for distinct functions related to active interoceptive inference, such as interoceptive introspection, interoceptive prediction, interoceptive selection, interoceptive precision and interoception flexibility. The insula-PFC-striatum parallel networks are hierarchically organized as follows. The lower level comprises the gINS-SMA-pStr network specialized for storage and quick generation habit-like interoceptive predictions. The mid-level comprises the dINS-DLPFC-mStr network specialized for model-based interoceptive predictions, and the highest level comprises the aINS-VMPFC-vStr network specialized for interoceptive exploration. Other neural systems provide additional functions to the interoceptive predictions of these networks, such as supervised interoceptive predictions by the cerebellum, social interoception by the TPJ, episodic interoception and declarative interoception by the hippocampus, and Pavlovian interoception conditioning by the amygdala. The dashed line represents ascending interoceptive prediction errors. The continuous lines represent descending interoceptive predictions. The black lines represent connections within the striatum circuitry. (b) Schematic representation of the neuroanatomical location of the brain structures supporting insula active interoceptive inference. SMA (supplementary motor area), DLPFC (dorsolateral prefrontal cortex), VMPFC (ventromedial prefrontal cortex), ACC (anterior cingulate cortex), gINS (granular insula), dINS (dysgranular insula), aINS (agranular insula), pStr (posterior striatum), mStr (dorsomedial striatum), vStr (ventral striatum), eGP (external globus pallidus), iGP (internal globus pallidus), THA (thalamus), vlSN (ventrolateral substantia nigra complex), mSN (medial substantia nigra complex), VTA (ventral tegmental area), SNc (substantia nigra pars compacta), CB (cerebellum), NTS (nucleus tractus solitarius), D1 (dopamine receptor of the direct pathway), D2 (dopamine receptor of the indirect pathway), BS (brainstem), SB (subcortical brain regions, e.g. amygdala), vTHA (visceral thalamus: VMpo, VMb, PV [figure 1]).CC BY · PubMed Central
Figure 3. (a) Common view of cortical interoceptive control. In this view, the insular cortex, especially its agranular region, together with limbic structures, e.g. amygdala and VMPFC, receive ascending visceral signals and send descending control signals to modulate the activity of visceral systems. (b) The IMAC model proposes a hierarchical architecture where forward connections (green arrows) transmit interoceptive prediction errors, computed at each level of the hierarchy, and backward connections (red arrows) generate interoceptive predictions of desired interoceptive states. In this hierarchical interoceptive architecture, deep brain systems (subcortical and brainstem areas) contain mesaceptions (autonomic reflex arcs) or 1st order representations of interoceptive predictions. The insular cortex contains metaceptions or 2nd order representations of mesaceptions, and the PFC contains 3rd order representations of insula metaceptions and implements introspection to guide adaptive interoceptive behaviors and generate the meaning and causes of interoceptive prediction errors, as well as the consequences of interoceptive prediction. Gradient colors represent hierarchy levels within the insula, PFC and striatum (green: low hierarchy; orange: intermediate hierarchy; red: high hierarchy). (c) Examples of parallel insula hierarchical interoceptive networks. Here, five networks and their putative roles are highlighted with interoceptive signals arriving from either the vagus nerve (VN) and area postrema (AP) or from the spinothalamic tract (STT). Abbreviations: NTS (nucleus tractus solitary), MRF (medullar and reticular formation), PBN (parabrachial nucleus), PAG (periaqueductal gray), HYP (hypothalamus), THA (thalamus), gINS (granular insula), aINS (agranular insula), VTA-SNc (dopaminergic ventral tegmental area and substantia nigra pars compacta), DR-MR (serotonergic dorsal and median raphe nuclei), Amyg (amygdala), Hb (habenula), Str (striatum). Green arrows represent ascending interoceptive prediction errors and red arrows represent descending interoceptive predictions.
Figure 3. (a) Common view of cortical interoceptive control. In this view, the insular cortex, especially its agranular region, together with limbic structures, e.g. amygdala and VMPFC, receive ascending visceral signals and send descending control signals to modulate the activity of visceral systems. (b) The IMAC model proposes a hierarchical architecture where forward connections (green arrows) transmit interoceptive prediction errors, computed at each level of the hierarchy, and backward connections (red arrows) generate interoceptive predictions of desired interoceptive states. In this hierarchical interoceptive architecture, deep brain systems (subcortical and brainstem areas) contain mesaceptions (autonomic reflex arcs) or 1st order representations of interoceptive predictions. The insular cortex contains metaceptions or 2nd order representations of mesaceptions, and the PFC contains 3rd order representations of insula metaceptions and implements introspection to guide adaptive interoceptive behaviors and generate the meaning and causes of interoceptive prediction errors, as well as the consequences of interoceptive prediction. Gradient colors represent hierarchy levels within the insula, PFC and striatum (green: low hierarchy; orange: intermediate hierarchy; red: high hierarchy). (c) Examples of parallel insula hierarchical interoceptive networks. Here, five networks and their putative roles are highlighted with interoceptive signals arriving from either the vagus nerve (VN) and area postrema (AP) or from the spinothalamic tract (STT). Abbreviations: NTS (nucleus tractus solitary), MRF (medullar and reticular formation), PBN (parabrachial nucleus), PAG (periaqueductal gray), HYP (hypothalamus), THA (thalamus), gINS (granular insula), aINS (agranular insula), VTA-SNc (dopaminergic ventral tegmental area and substantia nigra pars compacta), DR-MR (serotonergic dorsal and median raphe nuclei), Amyg (amygdala), Hb (habenula), Str (striatum). Green arrows represent ascending interoceptive prediction errors and red arrows represent descending interoceptive predictions.CC BY · PubMed Central

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Research works printed but not linked: 3

  1. Porges SW. 2011 The polyvagal theory: neurophysiological foundations of emotions, attachment, communication, and self-regulation (norton series on interpersonal neurobiology). New York, NY: WW Norton & Company.
  2. Fitts PM, Posner MI. 1967 Human performance. Oxford, England: Brooks/Cole.
  3. Stemmler G. 2004 Physiological processes during emotion. In The regulation of emotion, pp. 48-85. New York, NY: Psychology Press.

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Metadata

Authors
Fermin, A. S. R., Friston, K., & Yamawaki, S.
Affiliations
  • Hiroshima University (JP)
  • Wellcome Centre for Human Neuroimaging (GB)
Corresponding author
Fermin, Alan S. R.
ORCID
Venue
Royal Society Open Science
Publisher
The Royal Society
Published
2022-06
Volume
9
Issue
6
Pages
220226-220226
ISSN
2054-5703 (ISSN-L)
DOI
10.1098/rsos.220226
PMC
PMC9240682
OpenAlex
W4283707164
Cited by
101
References
329
Citations by year
2026: 31 · 2025: 22 · 2024: 28 · 2023: 16 · 2022: 2
FWCI
2.93
Type
journal article
Language
en
Open access
Licence
Locations
  • Royal Society Open Science (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • Wellcome Centre for Human Neuroimaging (205103/Z/16/Z)
  • Canada-UK Artificial Intelligence Initiative (ES/T01279X/1)
  • Japan Agency for Medical Research and Development (JP19dm0107093)
  • Center of Innovation Program (JPMJCA2208, JPMJCE1311)
  • Japan Society for the Promotion of Science (20309202, 20K07723, JPMJMS2296)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Embodied and Extended Cognition
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords
insula, interoception, prefrontal cortex, striatum, model-based control, depression

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